Concomitant radium-223 (Ra-223) and chemotherapy is a possible option for cancer patients (pts) with bone metastases (mets). Both treatments impact hematologic parameters, and myelosuppression risk during coadministration is unknown. This phase 1b study (NCT02442063) in cancer pts with bone mets evaluated the safety of Ra-223 + paclitaxel (PTX) and the mode of interaction between treatments regarding myelosuppression.
Eligible pts had a confirmed malignant solid tumor with ≥ 2 bone mets and were candidates for PTX treatment. Treatment included 7 PTX cycles (90 mg/m2 IV per wk as per local standard of care; 3 wk on/1wk off) combined with 6 Ra‑223 cycles (55 kBq/kg IV; 1 injection every 4 wk, starting at PTX cycle 2). The primary end point was percentage of pts with neutropenia and thrombocytopenia during treatment with Ra‑223 + PTX (cycles 2 and 3) vs PTX alone (cycle 1). A previously developed dose-exposure-response model describing the time course of PTX and Ra-223–induced suppression of absolute neutrophil counts was used to evaluate the mode of interaction (additive or synergistic) between Ra-223 and PTX.
Of 22 enrolled pts, 15 were treated; 13 completed cycles 1-3 and were included in the pharmacodynamics analysis. Tumors in treated pts were breast (7 pts), prostate (4 pts), bladder (1 pt), non‒small cell lung (1 pt), myxofibrosarcoma (1 pt), and neuroendocrine (1 pt). 7 pts had received ≥ 3 prior chemotherapy regimens. In the 13 pts who completed cycle 3, grade 3 neutropenia rates in cycles 2 and 3 were 31% and 8%, respectively, vs 23% in cycle 1; there were no cases of grade 4 neutropenia or grade 3/4 thrombocytopenia. No pts discontinued treatment due to toxicity from the treatment combination. Safety data for the breast cancer pt subset will be presented. The myelosuppression model showed an additive effect of Ra-223 to PTX-induced neutropenia, with an additional 10% average decrease in absolute neutrophil count vs PTX alone.
In pts with solid tumors and bone mets, Ra-223 was well tolerated when combined with PTX, with an additional 10% average decrease in neutrophil levels compared with PTX monotherapy. The combination should be explored further in pts with bone mets.
Clinical trial identification